Association of Genetically Predicted Serum Estradiol With Risk of Thromboembolism in Men: A Mendelian Randomization Study.
aromatase
estradiol
mendelian randomization
testosterone
thromboembolism
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
13 07 2021
13 07 2021
Historique:
received:
03
12
2020
pubmed:
12
3
2021
medline:
21
10
2021
entrez:
11
3
2021
Statut:
ppublish
Résumé
An association was recently reported between genetic markers related to high testosterone and increased risk of thromboembolism in men, but a possible causal role of estradiol for risk of thromboembolism in men remains unknown. This work aimed to determine whether endogenous estradiol has a causal role in thromboembolism in men. A 2-sample mendelian randomization study using gene-based genetic instruments assessed the association between endogenous estradiol genetically predicted by 22 variants in the aromatase CYP19A1 gene region and the risk of thromboembolism (5815 cases) in 170 593 unrelated men of White ancestry in the UK Biobank. The main outcome measure included thromboembolism based on self-reports, hospital episodes, and death. Endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with the risk of thromboembolism (odds ratio per SD increase in estradiol 0.74; 95% CI, 0.62-0.90). In contrast, genetic variants in the JMJD1C gene, used as a predictor of high endogenous testosterone, were associated with an increased risk of thromboembolism (odds ratio per SD increase in testosterone 1.39; 95% CI, 1.12-1.72). Subsequent explorative analyses evaluating potential repercussions of thromboembolism revealed that endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with the risk of ischemic stroke (0.68; 95% CI, 0.49-0.95) but not myocardial infarction (0.97; 95% CI, 0.84-1.13). Genetically predicted estradiol was inversely associated with the risk of thromboembolism and ischemic stroke in men. The ratio between testosterone and estradiol, determined by CYP19A1 activity, may contribute to the overall impact of sex steroids on thromboembolism in men.
Identifiants
pubmed: 33705547
pii: 6168433
doi: 10.1210/clinem/dgab164
pmc: PMC8277207
doi:
Substances chimiques
Testosterone
3XMK78S47O
Estradiol
4TI98Z838E
Aromatase
EC 1.14.14.1
CYP19A1 protein, human
EC 1.14.14.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3078-e3086Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.
Références
J Clin Endocrinol Metab. 2014 Dec;99(12):4565-73
pubmed: 25268392
J Clin Endocrinol Metab. 2019 Dec 1;104(12):6301-6315
pubmed: 31390027
Maturitas. 2013 Jul;75(3):282-8
pubmed: 23706278
Prostate Cancer Prostatic Dis. 2018 Nov;21(4):451-460
pubmed: 29988099
Stat Med. 2008 Apr 15;27(8):1133-63
pubmed: 17886233
J Clin Endocrinol Metab. 2019 Feb 1;104(2):433-442
pubmed: 30215726
J Clin Endocrinol Metab. 2013 Aug;98(8):3289-97
pubmed: 23775354
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Nat Commun. 2015 Sep 14;6:8111
pubmed: 26368830
Science. 2013 Jun 21;340(6139):1467-71
pubmed: 23722424
J Clin Endocrinol Metab. 2016 Jan;101(1):69-78
pubmed: 26509870
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
PLoS Genet. 2011 Oct;7(10):e1002313
pubmed: 21998597
BMJ. 2018 Jul 12;362:k601
pubmed: 30002074
Hum Mol Genet. 2012 Dec 1;21(23):5222-8
pubmed: 22936694
Ann Intern Med. 2020 Jan 21;172(2):105-118
pubmed: 31905375
Eur J Endocrinol. 2009 Sep;161(3):435-42
pubmed: 19542243
Eur J Endocrinol. 2012 Jun;166(6):983-91
pubmed: 22423144
Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):1004-8
pubmed: 17507629
Endocr Rev. 2003 Apr;24(2):152-82
pubmed: 12700178
JAMA. 2002 Jul 17;288(3):321-33
pubmed: 12117397
BMJ. 2008 May 31;336(7655):1227-31
pubmed: 18495631
Int J Epidemiol. 2015 Apr;44(2):512-25
pubmed: 26050253
BMJ. 2019 Mar 6;364:l476
pubmed: 30842065
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2016 Mar;59(3):361-7
pubmed: 26753864
Arch Intern Med. 2004 Oct 11;164(18):1965-76
pubmed: 15477430
J Am Coll Cardiol. 2011 Oct 11;58(16):1674-81
pubmed: 21982312
Thromb Haemost. 2018 Nov;118(11):1940-1950
pubmed: 30296818
J Clin Endocrinol Metab. 2018 Mar 1;103(3):991-1004
pubmed: 29325096
Stat Med. 2016 May 20;35(11):1880-906
pubmed: 26661904
Eur J Endocrinol. 2009 May;160(5):833-8
pubmed: 19208774
J Clin Endocrinol Metab. 2009 Jul;94(7):2353-9
pubmed: 19351733
J Thromb Haemost. 2014;12(3):297-305
pubmed: 24329981
Nat Rev Endocrinol. 2009 Aug;5(8):437-43
pubmed: 19528961
J Clin Endocrinol Metab. 2013 Jun;98(6):E1097-102
pubmed: 23633197
Bioinformatics. 2015 Nov 1;31(21):3555-7
pubmed: 26139635
J Clin Endocrinol Metab. 2006 Oct;91(10):3791-7
pubmed: 16882749
J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3078-e3086
pubmed: 33705547
Lancet. 2012 Mar 31;379(9822):1173-4
pubmed: 22463865
Fertil Steril. 2014 Feb;101(2):323-9
pubmed: 24485503
Stat Med. 2015 Sep 20;34(21):2926-40
pubmed: 25950993
Nat Rev Cardiol. 2019 Sep;16(9):555-574
pubmed: 31123340